The mechanism by which sulfasalazine (SASP) maintains remission in patients with ulcerative colitis is unknown. SASP or one of its major metabolites, 5-aminosalicylate (5-ASA) and sulfapyridine (SP), may have a direct effect on sodium and water transport in the colon, which could account for the ability of SASP to sustain clinical remission. The purpose of this project is to study the effects of SASP and its two major metabolites on sodium and water transport in rodent and human colon. Colonic sodium and water transport will be determined in normal rats and animals with experimentally-induced ulcerative colitis. Rats will be administered SASP, 5-ASA an SP by various routes of administration (oral ingestion, intravenous injection, and rectal instillation). The 3 compounds under study will also be perfused into rat colon with measurements of sodium and water fluxes. Human studies will evaluate changes of transmucosal potential difference (PD) in the distal colon after drug or metabolite ingestion. If an action on sodium transport is exhibited by SASP, SP, 5-ASA (administered singly or in combination), then the possible relationship between drug-induced sodium transport and intracellualr cyclic nucleotides, (cyclic AMP (cAMP) and cyclic GMP (cGMP), and prostaglandin E2 (PGE2) may be established in both rats and humans. The sulfonamide moiety is currently considered the metabolite of SASP that is responsible for most of the drug's toxicity. If 5-ASA appears to affect sodium and water flux, the theory that SASP functions only as a "vehicle" to deliver metabolites to the colon would be supported. It may then be possible to create pharmaceutical agents associated with fewer side-effects than SASP. If drug administration enhances sodium flux and if this increase is related to alterations in intracellular cAMP, cGMP, or PGE2, then the treatment of ulcerative colitis may be best achieved by agents which affect intracellular cyclic nucleotide or PGE2 content.